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Antidotal effects of methylene blue against cyanide neurological toxicity: in vivo and in vitro studies.
Annals of the New York Academy of Sciences ( IF 4.295 ) Pub Date : 2020-05-06 , DOI: 10.1111/nyas.14353
Philippe Haouzi,Marissa McCann,JuFang Wang,Xue-Qian Zhang,Jianliang Song,Ilker Sariyer,Diane Langford,Maryline Santerre,Nicole Tubbs,Annick Haouzi-Judenherc,Joseph Y Cheung

The aim of the present study was to determine whether methylene blue (MB) could directly oppose the neurological toxicity of a lethal cyanide (CN) intoxication. KCN, infused at the rate of 0.375 mg/kg/min intravenously, produced 100% lethality within 15 min in unanaesthetized rats (n = 12). MB at 10 (n = 5) or 20 mg/kg (n = 5), administered 3 min into CN infusion, allowed all animals to survive with no sequelae. No apnea and gasping were observed at 20 mg/kg MB (P < 0.001). The onset of coma was also significantly delayed and recovery from coma was shortened in a dose-dependent manner (median of 359 and 737 seconds, respectively, at 20 and 10 mg/kg). At 4 mg/kg MB (n = 5), all animals presented faster onset of coma and apnea and a longer period of recovery than at the highest doses (median 1344 seconds, P < 0.001). MB reversed NaCN-induced resting membrane potential depolarization and action potential depression in primary cultures of human fetal neurons intoxicated with CN. MB restored calcium homeostasis in the CN-intoxicated human SH-SY5Y neuroblastoma cell line. We conclude that MB mitigates the neuronal toxicity of CN in a dose-dependent manner, preventing the lethal depression of respiratory medullary neurons and fatal outcome.
更新日期:2020-05-06

 

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